In recent years, attention has been paid to regenerative medicine and regenerative medical care. Regenerative medical care is a type of medical care which by using cells attempts to regenerate the functions of biological tissues and organs which have fallen into functional disorder and dysfunction. In the field of regenerative medicine, almost all organs and tissues are targets for research, and they have already been put to practical use in some areas. Among them, an organ for which a technology for reconstructing self-regenerating tissues and organs has first been established is skin.
In the research field, regenerated skin in an in vitro system has so far been most widely used as a skin model because of its good handling property (Bell E, Ehrlich H P, Buttle D J, Nakatsuji T., Science Mar; 211 (4486): 1052-4, 1981, Tsunenaga M, Horii I, Kuroki T, Tissue Culture (20 (8), 282-285, 1994, Tsunenaga M, Kohno Y, Horii I, Yasumoto S, Huh N H, Tachikawa T, Yoshiki S, Kuroki T, Jpn J Cancer Res Mar; 85 (3): 238-44, 1994). However, it has the disadvantages in that the character thereof can be maintained only for a short period and that the durability against medicine is weak. As a human skin model which can be used to solve the above problems, there is technology in which human skin species are grafted directly onto immunodeficient animals (Yan H C, Juhasz I, Pilewski J, Murphy G F, Herlyn M, Albelda S M, J Clin Invest Mar; 91 (3): 986-96, 1993). This model is a skin model which is considerably close to human skin in situ. On the other hand, availability of fresh human skin is an important factor, and actual situations involve a practical problem in terms of available acquisition of fresh human skin.
A method for grafting a cultured human cell onto an immunodeficient animal to construct regenerated skin has been developed in order to overcome the situation described above. There are a plurality of such methods, and among them, attention has been paid to a spontaneous sorting method (for example, Japanese Patent Application Laid-Open (through PCT) No. 50589/2002, Wang C K, Nelson C F, Brinkman A M, Miller A C, Hoeffler W K, J Invest Dermatol. 2000, April; 114 (4): 674-80) in recent years. In this method, primarily cultured keratinocyte isolated from fresh human skin is mixed with a fibroblast to construct reconstructed skin on the skin of an experimental animal. This method provides the advantages that the cell can freely move and interaction between the cells is liable to be caused and that a structure closer to the skin of a living body is available.
However, according to the reports which have so far been given, evaluations are made only for 4 weeks after grafting at the longest, and at the end of this period, at least the surface's state does not reach a smooth state similar to that of human skin. In addition thereto, a decrease in the area of reconstructed skin with the passage of time, which is one of the typical and significant problems in constructing reconstructed skin, has not yet been solved (Boyce S T, Supp A P, Swope V B, Warden G D, J Invest Dermatol 2002 April; 118 (4): 556-7).